Lysosomes are off-shoots of the Golgi apparatus which contain the hydrolytic enzymes essential in lysosomal activity. These hydrolytic enzymes are originally produced in the endoplasmic reticulum and are then transported to the Golgi apparatus.
Lysosomes serve as the "stomach" or "garbage disposal" of eukaryotic cells. They are membrane-bound organelles containing approximately 50 different digestive enzymes (acid hydrolases) that break down numerous biological molecules. The interior pH of lysosomes is around 5. This acidic interior is what activates the enzymes, allowing them to function properly.
One function of lysosomes is to break down materials (i.e. macromolecules, bacterium, cell particles, and viruses) taken into the cell through a process called phagoocytosis. The process of phagocytosis occurs when a material is taken into the cell in vesicles called phagosomes that are created by pinched off sections of a cell's plasma membrane.
When a phagosome fuses with a lysosome, forming a phagolysosome, the hydrolytic enzymes inside the lysosome break down the material enveloped by the phagosome.
A lysosome breaks down materials into simpler components that are either used or excreted by a cell.
In addition, lysosomes are also involved in a process called autophagy in which a cell's own organelles are degraded. Old or unneeded organelles such as mitochondria are surrounded by a membrane that separates them from the rest of the cell and are then fused with a lysosome that proceeds to break down or digest the organelle.
(in this image, phagocytosis is represented at the top and autophagy is represented at the bottom)
Genetic Diseases
There are over 40 known genetic diseases associated with lysosomes generically called lysosome storage disorders. These various disorders arise when people lack certain lysosomal enzymes and therefore the lysosomes are unable to break down certain molecules. Since the lysosomes are unable to digest these molecules, they expand and as a result, impair cell functions. Here are two examples of lysosome storage disorders:
*Pompe Disease
This disease is caused by a build up of glycogen in lysosomes found in muscle cells. People with this disease inherit an abnormal gene from both their parents that interferes with their ability to produce the GAA enzyme which is needed in the break down of glycogen in lysosomes. The disease is divided into two categories: infantile-onset and late-onset. Pompe disease causes muscle weakness (most dangerously affecting the heart), leading to respiratory weakness.
*Gaucher Disease
This disease is caused by a build up of a lipid called glucocerebroside in bone marrow and organs (especially the spleen and the liver) due to insufficient enzyme activity. The issues associated with this disease can range from mild to severe including skeletal deterioration, anemia, and organ dysfunction caused by enlargement. There are two sub-categories of Guacher disease: Non-neuronopathic and nueronopathic.
**Research**
Author: Dr. Jeffery W. Kelly
Title of Paper: "Partial Restoration of Mutant Enzyme Homeostasis in Three Distinct Lysosomal Storage Disease Cell Lines by Altering Calcium Homeostasis"
Organization: The Scripps Research Institute
Funding Sources: National Institutes of Health, the Lita Annenberg Hazen Foundation, and the Skaggs Institute for Chemical Biology.
Author Summary (Abstract):
Lysosomes are organelles that contain more than 50 hydrolytic enzymes that break down macromolecules in a cell. A lysosomal storage disease results from deficient activity of one or more of these enzymes, leading to the accumulation of corresponding substrate(s). Currently, lysosomal storage diseases are treated by enzyme replacement therapy, which can be challenging because the enzyme has to enter the cell and the lysosome to function; in neuropathic diseases, enzyme replacement is not useful because recombinant enzymes do not enter the brain. We have shown that diltiazem and verapamil, potent US Food and Drug Administration–approved L-type Ca2+ channel blocker drugs, increased the endoplasmic reticulum (ER) folding capacity, trafficking, and activity of mutant lysosomal enzymes associated with three distinct lysosomal storage diseases. These compounds appear to function through a Ca2+ ion–mediated up-regulation of a subset of cytoplasmic and ER lumenal chaperones, possibly by activating signaling pathways that mitigate cellular stress. We have shown that increasing ER calcium levels appears to be a relatively selective strategy to partially restore mutant lysosomal enzyme homeostasis in diseases caused by the misfolding and degradation of nonhomologous mutant enzymes. Because diltiazem crosses the blood–brain barrier, it may be useful for the treatment of neuropathic lysosomal storage diseases, and possibly other loss-of-function diseases, although efficacy needs to be demonstrated.
Works Cited (Zara Bowden) Daigle, Scott N., and Cynthia K. Damer. “Lysosomes.” Biology Reference. Advameg Inc. 13 Oct. 2008 <http://www.biologyreference.com/La-Ma/Lysosomes.html>. Farabee, M. J., Dr. “Glossary .” Online Biology Book. 8 Aug. 2001. Estrella Mountain Community College. 13 Oct. 2008 <http://www.estrellamountain.edu/faculty/farabee/biobk/BioBookglossL.html>. Gaucher Care. Genzyme Corporation. 13 Oct. 2008 <http://www.gauchercare.com>. “How are lysosomes and peroxisomes produced?” Cell Biology Graduate Program. 5 Dec. 2003. UTMB. 13 Oct. 2008 <http://www.cellbio.utmb.edu/cellbio/lysosome.htm>. “Lysosomes.” McGraw-Hill Higher Education. The McGraw-Hill Companies Inc. . 13 Oct. 2008 <http://www.highered.mcgraw-hill.com/olc/dl/120067/bio01.swf>. “Online Medical Dictionary.” CancerWEB. 13 Oct. 2008 <http://www.cancerweb.ncl.ac.uk/omd/index.html>. “Phagocytosis.” The Free Dictionary by Farlex. Farlex Inc. 13 Oct. 2008 <http://www.medical-dictionary.thefreedictionary.com/phagocytosis>. “Plant and Animal Cell Animation.” CELLS alive. 13 Oct. 2008 <http://www.cellsalive.com/cells/cell_model.htm>. Pompe Community. Genzyme Corporation . 13 Oct. 2008 <http://www.pompe.com>. “Pompe Disease.” National Institute of Neurological Disorders and Stroke. 25 July 2007. National Institutes of Health. 13 Oct. 2008 <http://ww.ninds.nih.gov/disorders/pompe/pompe.htm>. Wikipedia. Wikimedia Foundation Inc. 13 Oct. 2008 <http://www.wikipedia.com>.
LYSOSOME'S:
Formation:
1. Primary lysosome's: Primary lysosome's are the original lysosome's formed by the enzymes from the RER that are transported to the trans end of the
Golgi apparatus. The Golgi puts the lysosomal enzymes into a vacuole for transportation around the cell
2. Secondary lysosome's: Secondary lysosome's are made when vacuoles form around a material or organelle and come in contact with the primary lysosome. There are two types of secondary lysosome's, one is formed by endocytocis and the second is formed by autophagy.
A. Endocytosis - There are three types of endocytosis. One is Phagocytocis and that is when the cell surrounds a solid particle, such as a bacterium, and puts it in a vacuole formed by the fusion of the cell membrane around the particle to form a phagosome.
Endocytocis
B. Autophagy - Process in which the cell destroys malfunctioning parts such as a mitochondria by enveloping it in a membrane.
Structure:
Usually spherical and about 0.5 µm in diameter
Lysosomes are vacuoles that contain hydrolytic enzymes that destroy cell parts and molecules within the cell. The acidic nature, caused by the hydrogen ion ATPase within the lysosomes membrane, helps to decompose materials because the hydrolytic enzymes only activate at low pH levels.
Function:
In a cell the lysosomes are a figurative garbage disposal for the cell. Lysosomes have three functions, one is to digest materials within the cell, such as ingested materials like bacteria, the second is to decompose old or deteriorating cell parts, and the third is to manage the products of receptor-mediated endocytocis (“process by which cells internalize molecules or viruses”).
Disease:
Tay-Sachs:
Tay-Sachs is a fatal disease that is caused by the buildup of a fatty substance called ganglioside GM2. The fatty substance buildup on tissues and nerve cells in the brain due to the lack of or inactivity of the digestive enzyme β-hexosaminidase A. β-hexosaminidase A is an enzyme found in lysosomes and breaks down lipids such as gangliosidei.
Hunters Syndrome:
Hunters Syndrome is caused by the inability to breakdown Glycosaminoglycan or GAG due to the deficiency of the enzyme Iduronate-2-sulfatase. Hunters results in distinct facial features, a large head, and an enlarged abdomen due to the buildup of GAG.
Research:
Lysosomes as Targets for Cancer Therapy
Nicole Fehrenbacher and Marja Jäättelä
Danish Cancer Society, Apoptosis Department, Institute of Cancer Biology, Copenhagen, Denmark Requests for reprints: Nicole Fehrenbacher, Danish Cancer Society, Apoptosis Department, Institute of Cancer Biology, Strandboulevarden 49, DK-2100 Copenhagen, Denmark. E-mail: nf@cancer.dk.
Tumor invasion and metastasis are associated with altered lysosomal trafficking and increased expression of the lysosomal proteases termed cathepsins. Emerging experimental evidence suggests that such alterations in lysosomes may form an "Achilles heel" for cancer cells by sensitizing them to death pathways involving lysosomal membrane permeabilization and the release of cathepsins into the cytosol. Here, we highlight recent results on cancer-related changes in the composition and function of lysosomes, focusing on possible implications for the development of novel cancer therapeutics that target tumor cell lysosomes.
Works Cited
Fehrenbacher, Nicole, and Marja Jäättelä. “Cancer Research.” Lysosomes as Targets for Cancer Therapy. 15 Apr. 2005. American Association for
Cancer Research. 22 Oct. 2008 <http://cancerres.aacrjournals.org/cgi/content/abstract/65/8/2993>.
“Hunter Syndrome.” Mayo Clinic. 9 Aug. 2008. Mayo Foundation for Medical Education and Research (MFMER). 25 Oct. 2008
<http://www.mayoclinic.com/health/hunter-syndrome/DS00790/DSECTION=causes/>.
Spurger, Linda. “Cell Biology Graduate Program.” University of Texas Medical Branch. 15 July 2004. U of Texas Medical Branch. 13 Oct. 2008
<http://cellbio.utmb.edu/cellbio/lysosome.htm>.
Lysosomes
Background
How lysosomes are formed:
Structure and Function (Lysosome video)
(in this image, phagocytosis is represented at the top and autophagy is represented at the bottom)
Genetic Diseases
There are over 40 known genetic diseases associated with lysosomes generically called lysosome storage disorders. These various disorders arise when people lack certain lysosomal enzymes and therefore the lysosomes are unable to break down certain molecules. Since the lysosomes are unable to digest these molecules, they expand and as a result, impair cell functions. Here are two examples of lysosome storage disorders:
*Pompe Disease
This disease is caused by a build up of glycogen in lysosomes found in muscle cells. People with this disease inherit an abnormal gene from both their parents that interferes with their ability to produce the GAA enzyme which is needed in the break down of glycogen in lysosomes. The disease is divided into two categories: infantile-onset and late-onset. Pompe disease causes muscle weakness (most dangerously affecting the heart), leading to respiratory weakness.
*Gaucher Disease
This disease is caused by a build up of a lipid called glucocerebroside in bone marrow and organs (especially the spleen and the liver) due to insufficient enzyme activity. The issues associated with this disease can range from mild to severe including skeletal deterioration, anemia, and organ dysfunction caused by enlargement. There are two sub-categories of Guacher disease: Non-neuronopathic and nueronopathic.
**Research**
Author: Dr. Jeffery W. Kelly
Title of Paper: "Partial Restoration of Mutant Enzyme Homeostasis in Three Distinct Lysosomal Storage Disease Cell Lines by Altering Calcium Homeostasis"
Organization: The Scripps Research Institute
Funding Sources: National Institutes of Health, the Lita Annenberg Hazen Foundation, and the Skaggs Institute for Chemical Biology.
Author Summary (Abstract):
Lysosomes are organelles that contain more than 50 hydrolytic enzymes that break down macromolecules in a cell. A lysosomal storage disease results from deficient activity of one or more of these enzymes, leading to the accumulation of corresponding substrate(s). Currently, lysosomal storage diseases are treated by enzyme replacement therapy, which can be challenging because the enzyme has to enter the cell and the lysosome to function; in neuropathic diseases, enzyme replacement is not useful because recombinant enzymes do not enter the brain. We have shown that diltiazem and verapamil, potent US Food and Drug Administration–approved L-type Ca2+ channel blocker drugs, increased the endoplasmic reticulum (ER) folding capacity, trafficking, and activity of mutant lysosomal enzymes associated with three distinct lysosomal storage diseases. These compounds appear to function through a Ca2+ ion–mediated up-regulation of a subset of cytoplasmic and ER lumenal chaperones, possibly by activating signaling pathways that mitigate cellular stress. We have shown that increasing ER calcium levels appears to be a relatively selective strategy to partially restore mutant lysosomal enzyme homeostasis in diseases caused by the misfolding and degradation of nonhomologous mutant enzymes. Because diltiazem crosses the blood–brain barrier, it may be useful for the treatment of neuropathic lysosomal storage diseases, and possibly other loss-of-function diseases, although efficacy needs to be demonstrated.
Works Cited (Zara Bowden)
Daigle, Scott N., and Cynthia K. Damer. “Lysosomes.” Biology Reference. Advameg Inc. 13 Oct. 2008 <http://www.biologyreference.com/La-Ma/Lysosomes.html>.
Farabee, M. J., Dr. “Glossary .” Online Biology Book. 8 Aug. 2001. Estrella Mountain Community College. 13 Oct. 2008 <http://www.estrellamountain.edu/faculty/farabee/biobk/BioBookglossL.html>.
Gaucher Care. Genzyme Corporation. 13 Oct. 2008 <http://www.gauchercare.com>.
“How are lysosomes and peroxisomes produced?” Cell Biology Graduate Program. 5 Dec. 2003. UTMB. 13 Oct. 2008 <http://www.cellbio.utmb.edu/cellbio/lysosome.htm>.
“Lysosomes.” McGraw-Hill Higher Education. The McGraw-Hill Companies Inc. . 13 Oct. 2008 <http://www.highered.mcgraw-hill.com/olc/dl/120067/bio01.swf>.
“Online Medical Dictionary.” CancerWEB. 13 Oct. 2008 <http://www.cancerweb.ncl.ac.uk/omd/index.html>.
“Phagocytosis.” The Free Dictionary by Farlex. Farlex Inc. 13 Oct. 2008 <http://www.medical-dictionary.thefreedictionary.com/phagocytosis>.
“Plant and Animal Cell Animation.” CELLS alive. 13 Oct. 2008 <http://www.cellsalive.com/cells/cell_model.htm>.
Pompe Community. Genzyme Corporation . 13 Oct. 2008 <http://www.pompe.com>.
“Pompe Disease.” National Institute of Neurological Disorders and Stroke. 25 July 2007. National Institutes of Health. 13 Oct. 2008 <http://ww.ninds.nih.gov/disorders/pompe/pompe.htm>.
Wikipedia. Wikimedia Foundation Inc. 13 Oct. 2008 <http://www.wikipedia.com>.
LYSOSOME'S:
Formation:
1. Primary lysosome's: Primary lysosome's are the original lysosome's formed by the enzymes from the RER that are transported to the trans end of the
Golgi apparatus. The Golgi puts the lysosomal enzymes into a vacuole for transportation around the cell
2. Secondary lysosome's: Secondary lysosome's are made when vacuoles form around a material or organelle and come in contact with the primary lysosome. There are two types of secondary lysosome's, one is formed by endocytocis and the second is formed by autophagy.
A. Endocytosis - There are three types of endocytosis. One is Phagocytocis and that is when the cell surrounds a solid particle, such as a bacterium, and puts it in a vacuole formed by the fusion of the cell membrane around the particle to form a phagosome.
B. Autophagy - Process in which the cell destroys malfunctioning parts such as a mitochondria by enveloping it in a membrane.
Structure:
Usually spherical and about 0.5 µm in diameter
Lysosomes are vacuoles that contain hydrolytic enzymes that destroy cell parts and molecules within the cell. The acidic nature, caused by the hydrogen ion ATPase within the lysosomes membrane, helps to decompose materials because the hydrolytic enzymes only activate at low pH levels.
Function:
In a cell the lysosomes are a figurative garbage disposal for the cell. Lysosomes have three functions, one is to digest materials within the cell, such as ingested materials like bacteria, the second is to decompose old or deteriorating cell parts, and the third is to manage the products of receptor-mediated endocytocis (“process by which cells internalize molecules or viruses”).
Disease:
Tay-Sachs:
Tay-Sachs is a fatal disease that is caused by the buildup of a fatty substance called ganglioside GM2. The fatty substance buildup on tissues and nerve cells in the brain due to the lack of or inactivity of the digestive enzyme β-hexosaminidase A. β-hexosaminidase A is an enzyme found in lysosomes and breaks down lipids such as gangliosidei.
Hunters Syndrome:
Hunters Syndrome is caused by the inability to breakdown Glycosaminoglycan or GAG due to the deficiency of the enzyme Iduronate-2-sulfatase. Hunters results in distinct facial features, a large head, and an enlarged abdomen due to the buildup of GAG.
Research:
Lysosomes as Targets for Cancer Therapy
Nicole Fehrenbacher and Marja JäätteläDanish Cancer Society, Apoptosis Department, Institute of Cancer Biology, Copenhagen, Denmark
Requests for reprints: Nicole Fehrenbacher, Danish Cancer Society, Apoptosis Department, Institute of Cancer Biology, Strandboulevarden 49, DK-2100 Copenhagen, Denmark. E-mail: nf@cancer.dk.
Tumor invasion and metastasis are associated with altered lysosomal trafficking and increased expression of the lysosomal proteases termed cathepsins. Emerging experimental evidence suggests that such alterations in lysosomes may form an "Achilles heel" for cancer cells by sensitizing them to death pathways involving lysosomal membrane permeabilization and the release of cathepsins into the cytosol. Here, we highlight recent results on cancer-related changes in the composition and function of lysosomes, focusing on possible implications for the development of novel cancer therapeutics that target tumor cell lysosomes.
Works Cited
Fehrenbacher, Nicole, and Marja Jäättelä. “Cancer Research.” Lysosomes as Targets for Cancer Therapy. 15 Apr. 2005. American Association for
Cancer Research. 22 Oct. 2008 <http://cancerres.aacrjournals.org/cgi/content/abstract/65/8/2993>.
“Hunter Syndrome.” Mayo Clinic. 9 Aug. 2008. Mayo Foundation for Medical Education and Research (MFMER). 25 Oct. 2008
<http://www.mayoclinic.com/health/hunter-syndrome/DS00790/DSECTION=causes/>.
“Lysosomes.” Science Online. Facts On File News Services. 25 Oct. 2008 <http://www.2facts.com/>.
“Lysosomes.” Wikipedia. 23 Oct. 2008. Wikipedia. 25 Oct. 2008 <http://en.wikipedia.org/wiki/Lysosomes>.
Spurger, Linda. “Cell Biology Graduate Program.” University of Texas Medical Branch. 15 July 2004. U of Texas Medical Branch. 13 Oct. 2008
<http://cellbio.utmb.edu/cellbio/lysosome.htm>.
Sullivan, Jim. “Cell Models.” Cells Alive. 2006. Quill Graphics. 25 Oct. 2008 <http://www.cellsalive.com/cells/3dcell.htm>.